15-101922634-C-G

Position:

• chr15-101922634-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The ENST00000650172.1(OR4F4):​c.480G>C​(p.Trp160Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 14)
• Consequence: OR4F4 ENST00000650172.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.622

Genes affected

OR4F4 (HGNC:8301): (olfactory receptor family 4 subfamily F member 4) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR4F4	ENST00000650172.1	c.480G>C	p.Trp160Cys	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes Cov.: 14

GnomAD4 exome Cov.: 11

GnomAD4 genome Cov.: 14

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2023

The c.426G>C (p.W142C) alteration is located in exon 1 (coding exon 1) of the OR4F4 gene. This alteration results from a G to C substitution at nucleotide position 426, causing the tryptophan (W) at amino acid position 142 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.087	T;.
Eigen	Benign	0.096
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Benign	-0.49	T
MutationAssessor	Pathogenic	2.9	M;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-13	D;.
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0	D;.
Polyphen		1.0	D;.
Vest4		0.35
MutPred		0.48		Loss of stability (P = 0.3983);.;
MVP		0.78
ClinPred		1.0	D
GERP RS		1.9
Varity_R		0.56
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-102462837;